Pharmacodynamic Effects and Predictive Biomarkers of Janus Kinases (JAK)/Signal Transducer and Activator of Transcription (STAT) Inhibition With Ruxolitinib in Operable Head and Neck Cancer: a Window Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Proportional Percent Change in Tumor Size by Group
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of ruxolitinib in patients with operable Head and neck squamous cell carcinoma (HNSCC) who are planned for definitive surgery.
详细描述
PRIMARY OBJECTIVES:
I. To identify baseline and/or pharmacodynamic biomarkers of response to ruxolitinib, based upon association with quantitative change in tumor size following 14-21 days of neoadjuvant ruxolitinib in patients with operable HNSCC as determined by quantitative change in Tumor size.
SECONDARY OBJECTIVES:
I. To describe the tolerability of brief neoadjuvant exposure to ruxolitinib II. To assess the effect of ruxolitinib on the tumoral Ki-67 proliferation index III. To evaluate additional candidate biomarkers of ruxolitinib response or resistance in HNSCC patients as determined by quantitative change in Tumor size,
OUTLINE:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed, primary or recurrent, head and neck squamous cell carcinoma, including variants. Patients must have at least one measureable lesion in accordance with RECIST 1.1 (tumor diameter ≥ 1 cm; short-axis lymph node diameter ≥ 1.5 cm) OR by caliper measurement (tumor diameter ≥ 1 cm). Any diagnostic pretreatment biopsy sample is acceptable including fine needle aspiration (FNA).
- •Primary tumors of any head and neck (oral cavity, oropharynx, hypopharynx, or larynx) site will be included.
- •Surgical resection of head and neck must be planned, either as primary treatment or salvage. Patients must have submitted adequate pretreatment archival or fresh tissue.
- •Age ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (See Appendix 1).
- •Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (sensitivity ≤ 25 human chorionic gonadotropin (HCG) IU/L) within 4 weeks prior to registration and will be repeated within 72 hours prior to the start of study drug administration.
- •Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 12 weeks after study drug is stopped. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
- •Adequate hematologic, renal and hepatic function, as defined by:
- •Absolute neutrophil count (ANC) ≥ 1,500/ul, platelets ≥ 150,000/ul.
- •Creatinine ≤ 1.5 x institutional upper limit of normal (ULN).
- •Bilirubin ≤ 1.5 x ULN, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN.
- •Have signed written informed consent
排除标准
- •Subjects who fail to meet the above criteria.
- •Prior therapy for head and neck cancer is allowed, and the number of treatments is not limited. However, any systemic therapy should have been completed at least 30 days prior to study enrollment. Any radiation to the head and neck should have been completed at least 30 days prior to study enrollment. Palliative radiation outside of the head and neck does not require a washout.
- •Pregnancy or breastfeeding. Women (patients or partners of male patients) of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy. All WOCBP must have a negative pregnancy test within 4 weeks prior to registration, and this must be repeated within 72 hours prior to first receiving ruxolitinib. If the pregnancy test is positive, the patient must not receive ruxolitinib and must not be enrolled in the study.
- •Any unresolved chronic toxicity ≥ grade 2 from previous anticancer therapy (except alopecia and anemia), according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
- •Current active infection requiring systemic antibiotic or antifungal therapy.
- •Acute hepatitis or known HIV.
- •Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.
- •New York Heart Association (NYHA) Class III or IV heart disease.
- •History of thromboembolic event or other condition currently requiring anticoagulation with warfarin (coumadin). Patients who are treated with low molecular weight heparin or fondaparinux are eligible.
- •History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease, diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies, or ongoing or recent (≤ 3 months) significant gastrointestinal bleeding
- •Concomitant Medications, any of the following should be considered for exclusion: Strong CYP3A4 inhibitors: (Patients must discontinue drug 7 days prior to starting ruxolitinib), including but not limited to boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, or voriconazole. In addition, patients will be instructed to avoid grapefruit or grapefruit juice, starfruit, or seville oranges.
- •Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
研究组 & 干预措施
Neoadjuvant Ruxolitinib
Participants will take 15 mg or 20 mg of ruxolitinib by mouth twice daily for up to 4 weeks during the pre-operative window for 14-21 days, or up to 28 days for delays in planned surgery. Dose will be assigned based on participant platelet count at baseline. The last dose will be taken the morning of planned surgery. Ruxolitinib will be dispensed in 5 mg tablets. Participants will either take three tables (15 mg) in the morning and evening, or four tablets in the morning and evening (20 mg). Participants will be asked to fill out a drug diary indicating when doses of study drug are taken and any side effects they experience.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Proportional Percent Change in Tumor Size by Group
时间窗: Up to 4 weeks
Measured clinical ruxolitinib response of quantitative change in tumor size measured as a proportional percent (range -100% to +100%) from baseline to day 14-21 by group.
次要结局
- Number of Participants With Treatment-related Adverse Events(Up to 12 weeks)
- Number of Participants With Documented Surgical Complications(Up to 12 weeks.)
- Median Length of Hospital Stay(Up to 12 weeks)
- Median Change in Ki-67 Proliferative Index Value(Up to 12 weeks)